Irvine, Calif., Sept. 14, 1998 - Researchers at UC Irvine's College of Medicine have found a possible new weapon for the AIDS arsenal: a chemical extracted from green coffee beans. The chemical is identical to substances found in medicinal plants that Bolivian shamans have used for more than 1,500 years to treat a variety of disorders. If further experiments prove successful, the researchers' findings could lead to development of an entirely new class of AIDS-fighting drugs.
The chemical, chicoric acid, comes from chicory, which is derived from coffee beans. Dr. Edward Robinson, professor of microbiology and pathology at UCI, and Peter King, a graduate student of microbiology, added chicoric acid to cells in the laboratory that were infected with HIV, the virus that causes AIDS. The chicoric acid appeared to halt the actions of a key enzyme called HIV integrase that helps HIV infect cells, Robinson and King report in the Sept. 11 Journal of Virology.
Chicoric acid originally was found in green coffee beans high in the Bolivian Andes Mountains, Robinson said. Robinson and his colleagues have been making extracts of more than 60 plants used as remedies by Kallawaya Indian shamans, and found that several-including chicoric acid-have an effect on the AIDS virus in the laboratory.
Their research, if successful, could lead to clinical trials to determine how well-and how safely-these new chemicals work in humans. "Knowing how these chemicals work would allow us to design different AIDS drugs for which HIV hasn't become resistant, and which may not be as toxic as some current drugs. This finding opens up a whole new avenue for AIDS research," Robinson said.
Over the past two years, studies by Robinson's group and other researchers showed that mixing various amounts of chicoric acid with extracted HIV integrase slowed the enzyme's activity, but researchers until now were unable to take the crucial step of demonstrating that the same anti-HIV action occurred within cells.
HIV integrase is one of three key enzymes that allow HIV to infect healthy cells and cause AIDS. The other two enzymes, HIV protease and HIV reverse transcriptase, have for several years been the targets of anti-AIDS "cocktails," which are mixtures of several chemicals that arrest the action of HIV and are now prescribed routinely for AIDS patients. "With the eventual addition of chemicals that inhibit HIV integrase as well as the other two enzymes, we can attack the three main enzymes used by HIV to spread through the body," King said.
In the laboratory, chicoric acid can inhibit HIV integrase at doses that are not toxic to cells, another hopeful sign of its promise in fighting AIDS. Currently, the cocktails used against the other two HIV enzymes are toxic to cells and have negative side effects, Robinson said.
Despite toxic side effects, multi-chemical cocktails are the most effective way known to combat AIDS, because HIV quickly resists individual chemical treatments. If chicoric acid is effective, it could benefit HIV therapy without adding more toxic chemicals to the cocktails. "The more chemicals you can add to the cocktail, the more effectively it will stop HIV infection," Robinson said.
Robinson and King found that chicoric acid works by halting the takeover of healthy cells by the HIV virus. HIV takes over healthy cells by weaving its viral genetic material in with the healthy cell's DNA. This process, called integration, results in HIV using the cell to rapidly make multiple copies of itself, furthering the progression of AIDS. Chicoric acid inhibits HIV integrase, the enzyme that aids this process, and grinds the rate of HIV integration to a near-standstill. Stopping the process of integration keeps HIV from reproducing and infecting other cells.
Robinson cautions that chicoric acid is not potent enough to act as an anti-AIDS drug on its own. "We want to make a synthetic chemical that inhibits HIV integrase like chicoric acid, but which is more potent than its natural form, so we could use it in humans against the disease," he said.
Any new chemical would have to undergo rigorous clinical tests for safety and effectiveness before it's ever included in an anti-AIDS "cocktail," Robinson noted.
Robinson, who has been a medical researcher at UCI since 1992, first heard of the Bolivian extracts in 1987 from an anthropologist friend. "He knew a lot about these shamans and said that the plants they used really seemed to work on people," Robinson said.
The plants were used to fight fungal infections, liver disorders and cancer, and Robinson suspected they might help him in his search for new ways to fight AIDS. "The green coffee beans seemed to work the best. Roasting them destroys the effect," he said. Robinson and his colleagues also have been looking at plants from other areas, such as Pakistan and China, in search of still more extracts that could be turned into anti-HIV chemicals.
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